There is today a trend towards minimally invasive techniques for administration or sampling of substances or cells to or from various organ systems. Most organs and tissues in the body can be reached by needles with or without ultrasonic or computerized tomography guidance and if this is not possible, open surgery is an option. Stereotactic delivery, assisted by modern imaging techniques, are also existing alternatives.
However, these techniques are not applicable for all organ systems, e.g. due to the limited resolution of the imaging modalities and sub-sequential planning of safe route at justifiable patient risk and radiation doses.
Moreover, there are some target areas in the body that are not accessible by known minimally invasive techniques and devices via safe routes. For such organs with less accessible anatomical location, parenchymal access can be associated with significant surgical risks.
The development of endovascular microcatheter techniques during the last years has opened a possibility to reach parts of the body that have been difficult to reach previously by conventional means by using arteries and veins as via the “internal routes” that they constitute. The potential of these techniques was recognized due to the possibility to do minimally invasive transplantations, such as disclosed in Bliss, T., R. Guzman, et al. (2007). “Cell transplantation therapy for stroke.” Stroke 38(2 Suppl): 817-26.
U.S. Pat. No. 6,602,241 of Transvascular Inc. discloses methods and apparatus for delivery of substances or apparatus to target sites located outside blood vessels. A vessel wall penetrating catheter is disclosed that is inserted into the vasculature, positioned and oriented within a blood vessel near a target extravascular site and a penetrator is advanced from the catheter so as to perform an outward penetration through the wall of the blood vessel in the direction of the target site. Thereafter, a delivery catheter is passed through a lumen of the penetrator to the target site. A desired substance or apparatus is then delivered to or obtained from the target site. In some applications, the penetrator may be retracted into the vessel wall penetrating catheter and the vessel wall penetrating catheter may be removed, leaving the delivery catheter in place for chronic or continuous delivery of substance(s) to and/or obtaining of information or samples from the target site. Alternatively, a delivery catheter having an occlusion member or balloon may be advanced into a vein or venule and the occlusion member or balloon may be used to occlude the lumen of the vein or venule during and after injection of a substance through the catheter, such that the substance will not be carried away by normal venous blood flow and will remain in the vein or venule for a sufficient period of time to have its intended effect, e.g. to enter adjacent tissues through capillary beds drained by that vein or venule.
However, the disclosure of U.S. Pat. No. 6,602,241 describes a system providing penetration of a vein, i.e. the low pressure side of the vasculature, leaving a catheter in position at the penetration site of the vein. The catheter is connected all the way through the vasculature to the entry point into the body or vasculature.
In addition, it appears that the system disclosed in U.S. Pat. No. 6,602,241 does not provide a satisfactory solution to avoid bleeding at the penetration side inside the body after completed treatment when the catheter is retracted. It is mentioned that a backflow of injected fluid may be prevented by injecting a suitable adhesive or embolizing material such as a cyanoacrylate, polyethylene glycol, hydrogel or fibrin glue through the catheter lumen as the catheter is being pulled back through the tissue tract, through which it was initially inserted.
However, this solution to avoid bleeding at the penetration site is not satisfactory from a clinical point of view as it is difficult to perform and to monitor the success thereof. In addition, the injection of adhesive or embolization material may induce thrombotic embolies or unintentionally occlude the delivery vessel completely. Furthermore, the use of adhesives is not feasible in arterial vessels due to the existing higher blood pressure pushing the adhesive material out of the penetration site into the surrounding tissue before the penetration site is closed.
Moreover, the vessel wall penetrating catheter disclosed in U.S. Pat. No. 6,602,241 is of such large size that it cannot navigate into the microvasculature, e.g. into the central nervous system (CNS). Furthermore, the vessel wall penetrating catheter body includes a rigid proximal section and an elongated flexible distal section joined to the proximal section, wherein the distal section is sized to be received within the coronary sinus (venous system). The catheter body also has a penetrator lumen accommodating a vessel wall penetrator, such as a hollow Nitinol (NiTi—an alloy of Nickel and Titanium) needle, advanceable out of a side exit port. The catheter body also has a guidewire lumen which extends to the distal end of the catheter body. In summary, the catheter comprises many components and is therefore of the aforementioned large size.
Hence, the vessel penetrating catheter disclosed in U.S. Pat. No. 6,602,241 is not suited for vascular navigation into the CNS or other similar small vessels in the body. The vessel wall penetrator body is, amongst other things due to the multi lumen design, so large that it would occlude such small vessels, which is highly undesired, and may be fatal to the CNS parenchyma supported by such an artery.
Other known techniques using stent connections between vessels comprise transjugular intrahepatic portosystemic shunts (TIPS), which is a technique to provide a permanent stent connection between large veins of the liver, e.g. the v. porta and the v. hepatic. This is an endovascular technique, using a radiologic procedure to place a stent in the middle of the liver to reroute the blood flow. The TIPS procedure is done using intravenous sedation or general anesthesia. During the procedure, an interventional radiologist makes a tunnel through the liver with a needle, connecting the portal vein, i.e. the vein that carries blood from the digestive organs to the liver, to one of the hepatic veins, i.e. the three veins that carry blood from the liver. A metal stent is placed in this tunnel to keep the track open. However, this endovascular technique is not suited for the arterial part of the body vascular system. Furthermore, it is not suited for use in microvessels, but in large vessels. In addition, a stent is left in place for keeping a permanent communication between vessels. Moreover, in practice the radiologist usually pushes and retracts the needle several times until the second vein is hit, which implies a risk for bleedings. The amount of bleeding that can occur can sometimes be life threatening needing costly patient monitoring in intensive care.
Similar unwanted multi penetration of a vessel wall with potential patient bleeding is potential while using an apparatus as disclosed in U.S. Pat. No. 6,302,870. The apparatus comprises a plurality of laterally flexible needles for reaching body cavities. The configuration of the apparatus is such that the wall of the blood vessel juxtaposed to the site of delivery is potentially circumferential penetrated by the several needle points. As the blood vessel wall becomes perforated a rupture in the wall may occur, in particular at the arterial side of the vascular system.
A further issue is when vascular walls are penetrated, e.g. by a needle, upon retraction of the needle, a compression of the exit site is needed in order to avoid bleeding. However, often it is not possible to provide a compression of such an exit site at conventionally difficult accessible target sites in a human or animal body.
Various needle tips may be found for example as disclosed in WO00/13728 or U.S. Pat. No. 5,092,848. Commonly these have in common the ability to penetrate into soft tissue and are disclosed to be permanently secured to the distal end of a delivery catheter. As the catheter is retracted the tip follows back with the catheter, leaving a transmural hole which hopefully will collapse sealing the channel in the vessel wall to the extravascular space. However, the ability to seal properly depends on e.g. the compliance of the tissue and the blood pressure in the vessel. A self sealing ability is not sufficient on the arterial side of the vascular system especially in areas where no bleeding is tolerated, e.g. in connection with CNS interventions.
Conventionally difficult accessible target sites in the body may not be reached with the aforementioned devices.
Hence, it is difficult to deliver substances to and/or from conventionally difficult accessible target sites in a human or animal body.
Microcatheters are for instance disclosed in WO03080167A2. However, a penetration of vessel walls is not anticipated or implementable with this type of microcatheter as the distal tip of the disclosed microcatheter is blunt, and the distal end portion is in addition flexible and has spiral cuts. This provides for a vascular navigation to target sites which are located far more remote in the vascular system than accessible with catheter based techniques aimed for transvascular access such as the technique disclosed in U.S. Pat. No. 6,602,241. Thus, extravascular target sites are not accessible for this kind of microcatheters.
Another microcatheter device disclosed in WO2007121143 has a tissue penetrating tip member. This device appears to be not suited for use in the microvasculature. The tip is constructed with electrodes to heat the tip facilitating advancement in the tissue. Potentially necrosis may occur. Moreover, a transluminal channel is created, which when the microcatheter is retracted, leaves a hole trough the vessel wall to the extravascular space. An undesired effect as e.g. hemorrhage, at least on the arterial side of the vascular system is likely to occur.
An issue needing a novel and inventive solution is thus delivery of substances to and/or from conventionally difficult accessible target sites in a human or animal body, such as the microvasculature, e.g. in the CNS or pancreas.
In addition, or alternatively, there is a need to provide a solution that prevents or avoids bleeding from a penetration site of a vessel wall at the target site upon completed delivery or extraction of the substances.
Furthermore, a device suitable to be used on both the venous and arterial side of the vascular system would be beneficial in the operating theater as less equipment systems would be necessary.